Anaplastic large cell lymphomas presented as bone lesions: a clinicopathologic study of six cases and review of the literature.

Non-Hodgkin's lymphomas uncommonly present as bone lesions. Most of these tumors are diffuse large B-cell lymphomas. Anaplastic large cell lymphoma (ALCL) presented as bone lesions is exceedingly rare. In this study, we describe six cases of ALCL that presented as solitary or multiple bone lesions. The average patient age was 33 years (range, 4 to 63 years) and the male to female ratio was 2:1. Fever and localized bone pain were the most frequent presenting symptoms. Radiologic examinations revealed osteolytic lesions in all cases, with three (50%) being multiple lesions and five (83%) involving the axial bones. All patients were initially assessed to have only bone involvement. Staging studies revealed mild cervical lymphadenopathy in one patient and no evidence of extraskeletal disease in the other five patients. Histologically, there was diffuse infiltration of one or more bones by large pleomorphic lymphoma cells. Immunohistochemical studies showed all six neoplasms were positive for CD30, EMA, and granzyme B. One case was of T-cell lineage, positive for CD3. One case was positive for the T-cell-associated antigen CD4. The remaining four cases were of null-cell type. In-situ hybridization for EBV was performed in five cases; all were negative. Despite the relatively low International Prognostic Index (IPI) of these patients (mean, 1.67; range, 1 to 3), the overall prognosis was relatively poor: three of six died of disease within 2 years of diagnosis, and two of six were alive with evidence of disease (follow-up, 6 mo to 2 years). Thus, compared to their nodal counterparts, ALCLs that present as bone lesions are distinguished by their uniform expression of EMA and granzyme B, and a relatively poor clinical outcome. Our results also suggest that ALK-1 expression in this clinical setting is not a favorable prognostic indicator.